Due to the rapid progress of science, a new definition of the human embryo has been proposed (2023)

W.When someone says the word embryo, what do you think of? Probably the image you've seen thousands of times in thousands of different newspaper articles: a translucent sphere swollen with cytoplasm being pricked with a microinjection needle under the light of a microscope. The generalization of in vitro fertilization, or in vitro fertilization, allowed new generations of people to become acquainted with what the early stages of human development entail.

But earlier this summerwhen scientists revealedNow they can create masses of stem cells in the lab that self-assemble into the same kind of structures that the embryos themselves build in the first few weeks, opening up every notion of the embryo we once had. Were these structures models of embryos, as some scientists call them, or something close to real embryos? How would anyone know when that line was crossed?

"The definition of a human embryo is not yet firmly established, it is constantly evolving with scientific progress," said Nicolas Rivron, a developmental biologist at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna. INperspectiveIn an article published Thursday in the journal Cell on, an international group of leading luminaries in the rapidly expanding field of synthetic embryology (or "stembriology" as it is sometimes called) argue that these latest scientific advances justify a new definition of the human embryo. which has no roots in its roots. in how it was created, but in what it can become.

"We think that because of this new pathway, it's becoming increasingly important to think about the embryo not in terms of how it came to be, but in terms of the potential it has to generate," Rivron told STAT.

He and his co-authors proposed a definition of embryos as "a group of human cells supported by elements having extra-embryonic and uterine functions which together have the potential to form a fetus".

In other words, embryo models can be considered embryos if they have the potential to survive eight weeks of gestation, contradicting a statement released earlier this year by an international group of stem cell scientists.

The first known use of the word in English dates back to the 14th century and is derived from the Greek word embryo meaning "that which grows". It was not until the 1870s, when a scientific consensus began to emerge on the function of eggs and sperm cells, that embryos began to be defined in the process of fertilization. For most of the 20th century, legal definitions of an embryo referred to a group of cells resulting from fertilization and covering this developing mass until it transformed into something with a heart, brain, and other organs, when it (about 56 days later) became a fetus.

However, in 1997 this definition became obsolete. Birthfeed the sheepHe showed the world that you don't need an egg or sperm to live and breathe. DNA from any cell can be dropped into an empty oocyte and a clone can be produced, avoiding fertilization altogether. This opened the possibility of using this technique, called somatic cell nuclear transfer, one day in humans.

O ile nam wiadomo,it never happened. However, there is a possibility that this could lead different nations to change their legal definitions of an embryo. Japan and Australia added a language in stages of development. The Netherlands, Belgium, and Germany, among others, eliminated the language of fertilization and instead embraced the idea of ​​potentiality: that an embryo was defined by its ability to produce a human being.

However, these definitions were often broad and vague. The result is an intricate global patchwork of regulations that leaves much ambiguity about what it means to be an embryo, said Hank Greely, director of the Center for Law and Life Sciences at Stanford University. "It really needs to be made clearer what the rules say."

It was into this legal vacuum that stembriology stepped in: combining stem cell biology with bioengineering to produce self-assembling, embryo-like masses that could be plate-grown, mass-grown, punctured, punctured, tracked, and quantified in real time. Scientists believe they will prove to be an extremely powerful tool for lifting the eyelids.The black box of early human development., shedding a new perspective on infertility, miscarriage and genetic diseases. They can also provide a more flexible and ethical alternative to human embryo testing, which has historically been restricted by regulations and IVF donor wishes.

As researchers like Rivron enter the field, they fear that the lack of legal clarity on embryos (and thus when an embryo model might become one) could jeopardize funding, provoke public backlash, and even unknowingly put scientists in prison. . His proposal is an attempt to avoid such effects while recognizing the radically new possibilities that lie behind these scientific breakthroughs.

"Right now, we know that these structures that we can form in the lab, these embryo models, are not embryos because they cannot form a newborn," Rivron said. “But if in the future they fall and prove to be capable, there is no reason for us to distinguish between them. We will have to raise our ethical standards for using them for research purposes.”

To determine potentiality, the authors also propose a developmental Turing test to determine whether a model human embryo is capable of becoming a living, breathing person. The ultimate test, of course, would be to get pregnant with one. However, existing bans on human reproductive cloning in at least 45 countries would likely preclude such a test on models made from stem cells. (The guidelines issued by the influential International Society for Stem Cell Research (ISSCR) also prohibit the transfer of any model of a human embryo into the uterus of a human or animal.)

Instead, Rivron and her colleagues propose a combination of middle-of-the-road measures, setting out the kind of experimental plan scientists could conduct to understand the likelihood of embryo models potentially becoming more than a few cells in a dish. These include creating embryo models of large animals such as pigs and monkeys and implanting them in these species to see if they can develop normally and produce fertile offspring of their own.

"I really appreciate that they're open to the possibility that some embryo models might one day deserve to be treated like embryos," Greely said. "Because the general reaction in the field was to make a hexadecimal mark and say, 'These are not embryos.'"

That was the message sent by the ISSCR earlier this summer. In a statement issued in June, the organization reiterated its support for research using embryo models and condemned the use of the term "synthetic embryo" to describe them. "The integrated embryo models are neither synthetic nor embryonic," the statement said. "While these models can reproduce aspects of the early development of the human embryo, they cannot and will not develop to the level of postnatal human development."

Rivron said it was in talks with the ISSCR to set up a formal working group to look at the issue. He hopes that the document will be the first step towards raising awareness among policy makers, scientific societies and ethics committees.

“The stakes are definitely high here,” said Insoo Hyun, a bioethics fellow at Harvard Medical School, member of the ISSCR ethics committee, and director of life sciences and public instruction at the Boston Museum of Science. "These definition issues are not trivial because they really matter to things like funding and even crime."

This is especially important in places where there are financial or legal restrictions on what can be done with the embryos. For example, in Canada, scientists can conduct experiments on donor embryos, but cannot create embryos specifically for research purposes. In the United States, there are no laws specifically regulating embryo research. However, a clause called the Dickey-Wicker Amendment prohibits the federal government from funding any research that intentionally creates, destroys, or damages human embryos.

This provision establishes a legal definition of the term "human embryo" that governs how the National Institutes of Health may allocate funding for research. Embryos are considered to be any organism not yet protected by human research legislation "derived by fertilization, parthenogenesis, cloning or any other means from one or more human gametes (sperm or egg) or human diploid cells" .

Hyun said it's possible that some embryo models fall under this definition, depending on how you interpret what an "organism" is. “We know the NIH was a bit surprised by this,” Hyun said. "They're still very shy because there's a lot of confusion about what to do with these models."

Lyric Jorgenson, acting director of the NIH Office of Science Policy, stated in a statement to STAT that the institutes do not anticipate changes to the definition of the Dickey-Wicker Amendment or NIH policy. However, he praised the Rivron team's efforts to come up with a definition of non-NIH-funded research "that reflects the current state of science."

"It will be very important that we continue to jointly evaluate these definitions as our technologies evolve, to ensure that our policies keep pace with the knowledge gained at the frontier of human biology," Jorgenson said.

Sarah Franklin, director of the Reproductive Sociology Research Group at the University of Cambridge in the UK, welcomed the work that Rivron and her colleagues are doing to bring these issues into wider discussion. "You've done your profession a favor by working hard to answer a really important question: do we need a new definition of the embryo?" she said. “However, I am not sure that this way of asking questions is the best way to get to where we need to be. It's not a question that fits particularly easily into policymaking efforts."

Instead of focusing on the ontological conundrum of what an embryo is, he would like social scientists to explore what the public thinks about acceptable and unacceptable uses. Franklin pointed out how little data is currently available on the public's views on embryo research, let alone on stem cell-based embryo models.

"I think we have to be careful not to assume we know what kind of hot topics will be around this case," he said. "This is the biggest missing piece of the puzzle right now." However, in her opinion, this is the element that can best help governments create clear and logical rules that reflect the values ​​of the societies in which they exist.

Hyun and Greely also worry that the new definition somehow raises more questions than it answers. The cell beads that IVF clinics transfer into the uterus do not yet contain the "elements with extraembryonic and uterine functions" described by Rivron and colleagues. They develop only after implantation. Does this mean that those entities that are now called embryos would no longer be embryos within the meaning of this definition? What about an embryo that has been implanted but has a deadly genetic condition like trisomy 8, meaning it has no chance of surviving past 20 weeks? Is it an embryo?

Echoing the views of Mary Warnock, who led the early development of British policy in this field, Franklin suggested that we might not be able to get a proper definition of the embryo.GOOD– biologically, ethically and legally. "But if we have one, then yes."All right"For enough people, we're going to get some legislation, not none," Franklin said. “We want to avoid a situation where there are no limits. That's something most people don't really want."